FP09.05 Driver Oncogenic Alterations and Indoor Radon in NSCLC Patients From the IFCT Biomarker Cohort: Bioradon France Study

Abstract

Introduction: Radon is a radioactive gas, considered as the leading cause of lung cancer in non-smokers. In a previous work, we studied the correlation between the estimation of radon concentration from the French Indoor Radon Map (Institut de Radioprotection et de Surete Nucleaire, IRSN) and the regional prevalence of driver alterations in a cohort of 116.424 NSCLC patients in France (Mezquita et al, WCLC 2018). The prevalence of driver oncogene alterations was significantly higher in high-radon areas but clinical data were not available. We aim to confirm this hypothesis in an annotated database of NSCLC patients with matched molecular data available for adjustment (Barlesi et al, Lancet 2016). Method(s): Retrospective assessment of patients with NSCLC tested for EGFR/BRAF/HER2/KRAS mutations (m) and ALK fusion from the 28 Platform led by the National Cancer Institute between Apr.2012 and Apr.2013, and included in the Biomarkers France dataset. We studied the association between the prevalence of driver oncogenic alterations (EGFR/ALK/BRAF/HER2/KRAS) and the radon mean concentration in the area where the patient was born according to the IRSN Map. Adjustment on age, gender and smoking was performed. Result(s): Out of 17664 patients, we analyzed 3994 with birthplace available: 63% males, 82% smokers, with a median age of 64 years [18-94]. Lung cancer tumors were mostly adenocarcinoma (76%), followed by other histologies (18%) and squamous (6%). By molecular alterations: 468 tumors harbor EGFRm (12%), 129 ALK (3%), 89 BRAFm (2%), 32 HER2m (1%), 985 KRASm (25%); 2273 wildtype or harbor other non-driver alterations (control; 57%). Adenocarcinoma histology (83.7% vs. 80.2%, p=0.0034), and non-smoker habit (19.5% vs. 16.5%, p=0.0251) were more common in radon high-risk group (comparatively at the low risk group). The mean radon concentration by birthplace was 74.36 Bq/m3 +/-53.28SD [range 16.6-622.3], and by molecular groups: EGFRm 72.49 Bq/m3 +/- 47.98 SD [16.6-461.4], ALK 80.24 Bq/m3 +/-55.22SD [19.3-384.7], BRAFm 73.22 Bq/m3 +/-47.86SD [19.3-319.3], HER2m 72.74 Bq/m3 +/-39.51SD Bq/m3 [27.8-231.3], KRASm 71.79 Bq/m3 +/-53.32SD [16.6-576.8] and control group 75.67 Bq/m3 +/- 54.5SD [16.6-622.3] (p=0.20). The prevalence of driver alterations was higher in high-radon areas (table 1; p=0.0472); but no significant difference was observed after adjustment on age, gender and smoking. [Formula presented] Conclusion(s): We observed a higher prevalence of driver oncogenic alterations in NSCLC patients born in high radon areas; but no significant difference was observed after adjustment on age, gender and smoker. This study warrants further research on radon gas and driver oncogenes. Keywords: radon, lung cancer, driver oncogenic alterationsCopyright © 2021